tert-butyl (2R,4R)-4-((tert-butyldiphenylsilyl)oxy)-2-ethynylpyrrolidine-1-carboxylate | 833473-79-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (2R,4R)-4-((tert-butyldiphenylsilyl)oxy)-2-ethynylpyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2R,4R)-4-[tert-butyl(diphenyl)silyl]oxy-2-ethynylpyrrolidine-1-carboxylate
• CAS: 833473-79-3
• 化学式: C₂₇H₃₅NO₃Si
• 分子量: 449.665
• InChiKey: ABRLUNULLFPOFJ-FCHUYYIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.57
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R,4R)-4-((tert-butyldiphenylsilyl)oxy)-2-ethynylpyrrolidine-1-carboxylate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以90%的产率得到tert-butyl (2R,4R)-2-ethynyl-4-hydroxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

  摘要：

  A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.023
• 作为产物：
  描述：

  tert-butyl (2R,4R)-4-((tert-butyldiphenylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate 、 (1-重氮基-2-氧代丙基)膦酸二甲酯 在 potassium carbonate 作用下， 生成 tert-butyl (2R,4R)-4-((tert-butyldiphenylsilyl)oxy)-2-ethynylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors

  摘要：

  A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.023

文献信息

• Peptide-to-Small Molecule: A Pharmacophore-Guided Small Molecule Lead Generation Strategy from High-Affinity Macrocyclic Peptides
  作者：Shuhei Yoshida、Shota Uehara、Noriyasu Kondo、Yu Takahashi、Shiho Yamamoto、Atsushi Kameda、Soichiro Kawagoe、Naoko Inoue、Masami Yamada、Norito Yoshimura、Yuki Tachibana

  DOI：10.1021/acs.jmedchem.2c00919

  日期：2022.8.11

  identification of high-affinity macrocyclic peptides for a wide range of targets; however, it is still challenging to achieve the desired activity and membrane permeability at the same time. Here, we propose a novel small molecule lead discovery strategy, ″Peptide-to-Small Molecule″, which is a combination of rapid identification of high-affinity macrocyclic peptides via peptide display screening followed

  最近的技术创新导致开发了用于快速识别各种靶标的高亲和力大环肽的方法；然而，同时实现所需的活性和膜渗透性仍然具有挑战性。在这里，我们提出了一种新的小分子先导发现策略，“肽到小分子”，它是通过肽展示筛选快速识别高亲和力大环肽，然后是药效团引导的小分子从头设计的组合，并证明使用烟酰胺N-甲基转移酶 (NNMT) 作为靶标的适用性。肽展示技术亲和选择鉴定大环肽1表现出良好的酶抑制活性但没有基于细胞的活性。此后，肽药效团引导的从头设计和进一步的基于结构的优化产生了高效和细胞活性小分子14（无细胞 IC 50 = 0.0011 μM，基于细胞的 IC 50 = 0.40 μM），表明这策略可能是药物发现的新选择。